Comprehensive Lipid NanoParticle (LNP) Formulation Development and cGMP Manufacturing
Lipid NanoParticle (LNP) formulation is essential for various applications in the field of drug delivery and gene therapy. LNPs encapsulate and deliver therapeutic molecules, such as drugs or genetic material, to specific target cells or tissues in the body.
Our LNP development offering incorporates various technologies such as microfluidics and jet impingement, along with proper diafiltration / concentration. This allows you to manufacture targeted nanoparticle-formulated drugs, encapsulating your biological payload (e.g. mRNA, RNA, and oligonucleotides).
With our recently established GMP LNP manufacturing plant, your project will benefit from our complementary services for consecutive LNP formulation and batch-filling processes, all under one roof. This integrated approach helps minimize production time for your clinical material to ensure a more streamlined and effective process.
The Essentials of LNPs
LNPs are similar to liposomes, but differ in their composition and function. While liposomes are typically composed of phospholipids and sphingolipids that form a spherical lipid bi-layer with a hollow core, LNPs are usually smaller than 100 nm and composed of 4 lipids: cationic (or ionizable) lipids, phospholipids, sterols (such as non-animal origin cholesterol e.g Botanichol®) and lipid-anchored PEGylated phospholipids.
When combined using the appropriate LNP assembly technology, filterable nanoparticles are produced that can encapsulate a broad variety of genetic payloads such as Sa/si/micro RNA, Antisense Oligonucleotides (ASO), pDNA* and mRNA*, including that of CRISPR-Cas9. LNPs have been used in clinical trials and some have been commercially launched in a wide variety of therapeutic areas, most notably vaccines, oncology and metabolic diseases.
*Via partnership with Wacker Biotech
Each of these lipids has a distinct function:
- Cationic or ionizable lipid: interacts with nucleic acids, enhances cellular internalization
- Phospholipid (helper lipid): forms the surface membrane of LNPs
- Sterol: enhances membrane fluidity
- PEGylated phospholipid: increased stability, prevention of aggregation, increased half-life
LNP Assembly Technologies
To achieve high encapsulation efficiency, we use two well-established LNP assembly and mixing technologies that are proven and scalable from development to clinical and commercial activities:
- Impingement Jet Mixing (Knauer)
- Microfluidics (PNI – part of Cytiva)
Both technologies use the same principle for the formation of LNPs:
- Formed by a quick increase in the polarity of the environment induced by the rapid mixing of the two miscible high-velocity phases. This rapid mixing induces the supersaturation of lipid molecules
- Self-assembly into the desired structure without the wasteful need for size‐reduction methods
LNP Characterization
We use many analytical methods to characterize LNPs, including:
- The determination of particle size
- Distribution & z-potential encapsulation efficiency
- Lipid identity & concentration
- API identity & concentration
- Polydispersity index
These characterization methods, as well as full microbiological tests such as bioburden, endotoxin and sterility, are all performed in-house at our cGMP sterile injectable facility.
Proven LNP Formulation and Commercialization Pathway
To enable the capabilities needed to support your evolving mRNA and x-RNA drug strategies, we continue to invest in advanced LNP formulation technologies and sterile injectable manufacturing services, including:
- Expanded R&D laboratory, LNP formulation & analytical characterization capabilities
- Flexible & scalable cGMP LNP formulation for clinical to commercial supply
- Fully approved LNP manufacturing site able to produce drug products from clinical to commercial stage**
**As from Q2 2024
Your Benefits Include:
- Integrated offering for lipid supply, oligo supply and mRNA /pDNA supply*
- LNP formulation development, cGMP manufacturing and fill & finish at one site
- Fully scalable from development to commercialization
*Via partnership with Wacker Biotech
Integrated LNP Supply
CordenPharma offers cost-effective, end-to-end solutions for the fully-integrated supply of all products and processes needed for the formulation development and cGMP production of Lipid NanoParticle-based drug delivery systems:
- Standard and custom lipid manufacturing
- Sa/si/micro RNA, oligonucleotide, pDNA* and mRNA synthesis*
- Pre-formulation screening (including lipids)
- LNP formulation and process development
- LNP process scale-up and cGMP manufacture
- Sterile injectable drug product manufacturing of LNPs
*Via partnership with Wacker Biotech
Want to find out more?
Get in touch with our team of experts to explore bespoke end-to-end CDMO support of your complete drug lifecycle
at any scale.